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Socialization is an adaptive behavior during the early stages of life because it helps young animals become independent and determines healthy adult social behavior. Therefore, it is probable that the brain areas involved in the processing of social stimuli are more sensitive to social novelty during early life stages. To test this hypothesis, four groups of young male rats were exposed to different socioenvironmental stimuli; nonsocial physical novelty, social familiarity, social novelty, and a control group which received no stimulation. After stimuli exposure, brains were fixed and cut in coronal sections for c-Fos immunohistochemistry. The number of c-Fos-immunoreactive (c-Fos-ir) neurons in the paraventricular nucleus and supraoptic nucleus, the main producers of oxytocin and vasopressin, was compared, as well as in the nucleus accumbens and ventral pallidum, the main areas involved in reinforced behavior. A significantly higher number of c-Fos-ir neurons were found in animals exposed to social novelty in all areas, except in the supraoptic nucleus. In particular, the increase in c-Fos-ir in the paraventricular nucleus seems to be selective in response to social novelty, while the increase of c-Fos-ir in the nucleus accumbens and ventral pallidum suggests that social novelty during youth is a highly rewarding stimulus compared with social familiarity and nonsocial physical novelty.

Maternal separation has been shown to disrupt proper brain development and maturation, having profound consequences on the neuroendocrine systems in charge of the stress response, and has been shown to induce behavioral and cognitive abnormalities. At the behavioral level, maternal separation has been shown to increase offensive play-fighting in juvenile individuals and reduce social interest in adulthood. Since most of the studies that have evaluated the consequences of maternal separation on social behavior have focused on behavioral analysis, there is a need for a further understanding of the neuronal mechanisms underlying the changes in social behavior induced by maternal separation. Therefore, the aim of the present research was to assess the long-term effects of maternal separation on social interaction behavior and to assess the activity of several brain regions involved in the processing of social cues and reward upon social novelty exposure, using c-Fos immunohistochemistry as a marker of neuronal activity. Male Wistar rats were subjected to 4 h maternal separation during the neonatal period, 9:00 h–13:00 h from postnatal day 1 to 21, and exposed to social novelty during adulthood. After social novelty exposure, brains were fixed and coronal sections of the medial amygdala, lateral septum (LS), paraventricular nucleus of the hypothalamus, nucleus accumbens, and medial prefrontal cortex were obtained for c-Fos immunohistochemistry. Maternally separated rats spent less time investigating the novel peer, suggesting that maternal separation reduces social approach motivation. Furthermore, maternal separation reduced the number of c-Fos positive cells of the medial amygdala, paraventricular nucleus of the hypothalamus, LS, nucleus accumbens, and medial prefrontal cortex upon social novelty exposure. These findings suggest that maternal separation can reduce the plastic capacity of several brain nuclei, which constitute a physiological basis for the emergence of behavioral disorders presented later in life reported to be linked to early life adversity.

Food reward has been studied with highly palatable stimuli that come from natural additives such as sucrose. The most common food additive is sucralose, a noncaloric sweetener present in many food products of daily intake. The role of anandamide [N-arachidonylethanolamide (AEA)], an endogenous cannabinoid, has been widely studied in food behavior. Studies have shown that cannabinoids, such as AEA, 2-Arachidonilglycerol, and Tetrahydrocannabinol, can provoke hyperphagia, because they enhance the preference and intake of sweet and high-fat food. Taste perception is mediated by receptors taste type 1 receptor 3 (T1R3); therefore, there could be a synergistic effect between receptors CB1 and T1R3. This could explain why cannabinoids could change sweet taste perception and therefore the activity of neural nuclei involved in taste and reward. In this study, we evaluated the activity of dopaminergic nuclei implicated in food reward after the chronic administration of AEA (0.5 mg/kg bw) and sucralose intake (0.02%). We analyzed the expression of ΔFosB by immunohistochemistry. Our results show that the chronic administration of AEA and sucralose intake induces an overexpression of ΔFosB in the infralimbic cortex (Cx), nucleus accumbens (NAc) core, shell, and central nucleus of amygdala (Amy). These results suggest that the possible interaction between receptors CB1 and T1R3 has consequences not only in taste perception but also that AEA intervenes in the activity of dopaminergic nuclei such as the NAc, and that the chronic administration AEA and sucralose intake induce long-term changes in the reward system.